الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
alproic acid (VPA) is anti-epileptic and mood stabilizer drug that induces autism spectrum disorder (ASD). Canagliflozin was proved to have a neuroprotective effect. Therefore, the current study was conducted to examine the effect of Canagliflozin focusing on the canonical Wnt/ꞵ-Catenin pathway and its effect on various behaviors of rats as a possible mechanism in protection against VPA-induced autism. The effect of Canagliflozin on sociability and social preference, locomotor activity, repetitive and stereotypic behaviors, and anxiety-like behaviors were observed. Furthermore, the effect of Canagliflozin on gene and protein expression of glucose transporter-1 (GLUT-1), phosphatase and tensin homolog (PTEN), peroxisome proliferator-activated receptor-gamma (PPAR-γ), lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase (PDK), cellular Myeloctomatosis (c-Myc) and tissue level of acetylcholine (ACh) were evaluated. VPA was injected subcutaneously (SC) to rat pups at a dose of 300 mg/kg, twice daily
on a postnatal day-2 (PD-2), PD-3, and once on PD-4. Oral administration of Canagliflozin (5, 7.5, and 10mg/Kg/day) starting from the first day of VPA injection for 21 days, attenuated the severity of VPA-induced autism, enhanced most of the impaired behaviors and the degenerative histopathological features of the brain compared to VPA group. In addition, Canagliflozin suppressed expression of LDHA, PDK, c-Myc genes, and GLUT-1 protein expression compared to the VPA group. On the other hand, Cana enhanced gene expression of PPAR-γ, PTEN protein expression, and ACh level in brain tissues compared to the VPA group. The present study concluded that Canagliflozin may exhibit a protective effect against VPA-induced autism.
Key words:
Valproic acid; Canagliflozin; Wnt/ꞵ-Catenin pathway; Autism